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1.
Viruses ; 16(5)2024 05 08.
Article in English | MEDLINE | ID: mdl-38793625

ABSTRACT

INTRODUCTION: Hepatitis E virus (HEV) genotype 3 is the major cause of acute viral hepatitis in several European countries. It is acquired mainly by ingesting contaminated pork, but has also been reported to be transmitted through blood transfusion. Although most HEV infections, including those via blood products, are usually self-limiting, they may become chronic in immunocompromised persons. It is thus essential to identify HEV-infected blood donations to prevent transmission to vulnerable recipients. AIMS: Prior to the decision whether to introduce HEV RNA screening for all Swiss blood donations, a 2-year nationwide prevalence study was conducted. METHODS: All blood donations were screened in pools of 12-24 samples at five regional blood donation services, and HEV RNA-positive pools were subsequently resolved to the individual donation index donation (X). The viral load, HEV IgG and IgM serology, and HEV genotype were determined. Follow-up investigations were conducted on future control donations (X + 1) and previous archived donations of the donor (X - 1) where available. RESULTS: Between October 2018 and September 2020, 541,349 blood donations were screened and 125 confirmed positive donations were identified (prevalence 1:4331 donations). At the time of blood donation, the HEV RNA-positive individuals were symptom-free. The median viral load was 554 IU/mL (range: 2.01-2,500,000 IU/mL). Men (88; 70%) were more frequently infected than women (37; 30%), as compared with the sex distribution in the Swiss donor population (57% male/43% female, p < 0.01). Of the 106 genotyped cases (85%), all belonged to genotype 3. Two HEV sub-genotypes predominated; 3h3 (formerly 3s) and 3c. The remaining sub-genotypes are all known to circulate in Europe. Five 3ra genotypes were identified, this being a variant associated with rabbits. In total, 85 (68%) X donations were negative for HEV IgM and IgG. The remaining 40 (32%) were positive for HEV IgG and/or IgM, and consistent with an active infection. We found no markers of previous HEV in 87 of the 89 available and analyzed archive samples (X - 1). Two donors were HEV IgG-positive in the X - 1 donation suggesting insufficient immunity to prevent HEV reinfection. Time of collection of the 90 (72%) analyzed X + 1 donations varied between 2.9 and 101.9 weeks (median of 35 weeks) after X donation. As expected, none of those tested were positive for HEV RNA. Most donors (89; 99%) were positive for anti-HEV lgG/lgM (i.e., seroconversion). HEV lgM-positivity (23; 26%) indicates an often-long persistence of lgM antibodies post-HEV infection. CONCLUSION: The data collected during the first year of the study provided the basis for the decision to establish mandatory HEV RNA universal screening of all Swiss blood donations in minipools, a vital step in providing safer blood for all recipients, especially those who are immunosuppressed.


Subject(s)
Blood Donors , Genotype , Hepatitis E virus , Hepatitis E , RNA, Viral , Humans , Hepatitis E/epidemiology , Hepatitis E/transmission , Hepatitis E/virology , Blood Donors/statistics & numerical data , Switzerland/epidemiology , Hepatitis E virus/genetics , Hepatitis E virus/immunology , Hepatitis E virus/classification , Hepatitis E virus/isolation & purification , Male , Female , Adult , Prevalence , Middle Aged , RNA, Viral/genetics , RNA, Viral/blood , Hepatitis Antibodies/blood , Immunoglobulin M/blood , Young Adult , Immunoglobulin G/blood , Viral Load , Aged , Adolescent
2.
Infect Genet Evol ; 121: 105602, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38734397

ABSTRACT

Hepatitis E, caused by the hepatitis E virus (HEV), is a global public health issue. Low similarity between the gene sequences of mouse and human HEV led to the belief that the risk of human infection was low. Recent reports of chronic and acute hepatitis E caused by murine HEV infection in humans in Hong Kong have raised global concerns. Therefore, it is crucial to investigate the epidemiology and prevalence of HEV in China. We comprehensively analyzed different rodent HEV strains to understand rocahepevirus occurrence in Hubei Province, China. The HEV positivity rate for was 6.43% (73/1136). We identified seven near-full-length rocahepevirus strains and detected rat HEV antigens in tissues from different mouse species. HEV has extensive tissue tropism and a high viral load in the liver. We highlight the genetic diversity of HEVs in rodents and underscore the importance of paying attention to their variation and evolution.


Subject(s)
Hepatitis E virus , Hepatitis E , Phylogeny , Hepatitis E virus/genetics , Hepatitis E virus/classification , Animals , China/epidemiology , Hepatitis E/epidemiology , Hepatitis E/veterinary , Hepatitis E/virology , Prevalence , Mice , Rodentia/virology , Rats , Animals, Wild/virology , Genetic Variation
3.
Viruses ; 16(4)2024 04 03.
Article in English | MEDLINE | ID: mdl-38675900

ABSTRACT

Hepatitis E virus (HEV) is the main cause of acute hepatitis in humans worldwide and is responsible for a large number of outbreaks especially in Africa. Human infections are mainly caused by genotypes 1 and 2 of the genus Paslahepevirus, which are exclusively associated with humans. In contrast, viruses of genotypes 3 and 4 are zoonotic and have their main reservoir in domestic and wild pigs, from which they can be transmitted to humans primarily through the consumption of meat products. Both genotypes 3 and 4 are widespread in Europe, Asia, and North America and lead to sporadic cases of hepatitis E. However, there is little information available on the prevalence of these genotypes and possible transmission routes from animal reservoirs to humans in African countries. We therefore analysed 1086 pig sera collected in 2016/2017 in four districts in Sierra Leone for antibodies against HEV using a newly designed in-house ELISA. In addition, the samples were also analysed for HEV RNA by quantitative real-time RT-PCR. The overall seroprevalence in Sierra Leone was low with only 44 positive sera and a prevalence of 4.0%. Two serum pools were RT-PCR-positive and recovered partial sequences clustered into the genotype 3 (HEV-3) of the order Paslahepevirus, species Paslahepevirus balayani. The results are the first evidence of HEV-3 infection in pigs from Sierra Leone and demonstrate a low circulation of the virus in these animals to date. Further studies should include an examination of humans, especially those with close contact with pigs and porcine products, as well as environmental sampling to evaluate public health effects within the framework of a One Health approach.


Subject(s)
Genotype , Hepatitis E virus , Hepatitis E , Phylogeny , Swine Diseases , Animals , Hepatitis E/epidemiology , Hepatitis E/veterinary , Hepatitis E/virology , Hepatitis E virus/genetics , Hepatitis E virus/classification , Hepatitis E virus/isolation & purification , Hepatitis E virus/immunology , Seroepidemiologic Studies , Swine , Swine Diseases/virology , Swine Diseases/epidemiology , Sierra Leone/epidemiology , Hepatitis Antibodies/blood , RNA, Viral/genetics , Sus scrofa/virology , Humans
4.
Int J Food Microbiol ; 417: 110682, 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38626694

ABSTRACT

Hepatitis E infection is typically caused by contaminated water or food. In July and August 2022, an outbreak of hepatitis E was reported in a nursing home in Zhejiang Province, China. Local authorities and workers took immediate actions to confirm the outbreak, investigated the sources of infection and routes of transmission, took measures to terminate the outbreak, and summarized the lessons learned. An epidemiological investigation was conducted on all individuals in the nursing home, including demographic information, clinical symptoms, history of dietary, water intake and contact. Stool and blood samples were collected from these populations for laboratory examinations. The hygiene environment of the nursing home was also investigated. A case-control study was conducted to identify the risk factors for this outbreak. Of the 722 subjects in the nursing home, 77 were diagnosed with hepatitis E, for an attack rate of 10.66 %. Among them, 18 (23.38 %, 18/77) individuals had symptoms such as jaundice, fever, and loss of appetite and were defined as the population with hepatitis E. The average age of people infected with hepatitis E virus (HEV) was 59.96 years and the attack rate of hepatitis E among women (12.02 %, 59/491) was greater than that among men (7.79 %, 18/231). The rate was the highest among caregivers (22.22 %, 32/144) and lowest among logistics personnel (6.25 %, 2/32); however, these differences were not statistically significant (P > 0.05). Laboratory sequencing results indicated that the genotype of this hepatitis E outbreak was 4d. A case-control study showed that consuming pig liver (odds ratio (OR) = 7.50; 95 % confidence interval [CI]: 3.84-16.14, P < 0.001) and consuming raw fruits and vegetables (OR = 5.92; 95 % CI: 1.74-37.13, P = 0.017) were risk factors for this outbreak of Hepatitis E. Moreover, a monitoring video showed that the canteen personnel did not separate raw and cooked foods, and pig livers were cooked for only 2 min and 10 s. Approximately 1 month after the outbreak, an emergency vaccination for HEV was administered. No new cases were reported after two long incubation periods (approximately 4 months). The outbreak of HEV genotype 4d was likely caused by consuming undercooked pig liver, resulting in an attack rate of 10.66 %. This was related to the rapid stir-frying cooking method and the hygiene habit of not separating raw and cooked foods.


Subject(s)
Cooking , Hepatitis E , Nursing Homes , Pork Meat , Hepatitis E virus/classification , Hepatitis E virus/genetics , Hepatitis E/epidemiology , Hepatitis E/transmission , Hepatitis E/virology , Genotype , China/epidemiology , Pork Meat/virology , Liver/virology , Humans , Male , Female , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Risk Factors , Phylogeny
5.
Virus Res ; 344: 199364, 2024 06.
Article in English | MEDLINE | ID: mdl-38522562

ABSTRACT

The hepatitis E virus (HEV) can cause acute and chronic hepatitis in humans. Whereas HEV genotypes 1-4 of species Paslahepevirus balayani are commonly found in humans, infections with ratHEV (species Rocahepevirus ratti) were previously considered to be restricted to rats. However, several cases of human ratHEV infections have been described recently. To investigate the zoonotic potential of this virus, a genomic clone was constructed here based on sequence data of ratHEV strain pt2, originally identified in a human patient with acute hepatitis from Hongkong. For comparison, genomic clones of ratHEV strain R63 from a rat and of HEV genotype 3 strain 47832mc from a human patient were used. After transfection of in vitro-transcribed RNA from the genomic clones into the human hepatoma cell line HuH-7-Lunet BLR, virus replication was shown for all strains by increasing genome copy numbers in cell culture supernatants. These cells developed persistent virus infections, and virus particles in the culture supernatant as well as viral antigen within the cells were demonstrated. All three generated virus strains successfully infected fresh HuH-7-Lunet BLR cells. In contrast, the human hepatoma cell lines HuH-7 and PLC/PRF/5 could only be infected with the genotype 3 strain and to a lesser extent with ratHEV strain R63. Infection of the rat-derived hepatoma cell lines clone 9, MH1C1 and H-4-II-E did not result in efficient virus replication for either strain. The results indicate that ratHEV strains from rats and humans can infect human hepatoma cells. The replication efficiency is strongly dependent on the cell line and virus strain. The investigated rat hepatoma cell lines could not be infected and other rat-derived cells should be tested in future to identify permissive cell lines from rats. The developed genomic clone can represent a useful tool for future research investigating pathogenicity and zoonotic potential of ratHEV.


Subject(s)
Hepatitis E virus , Virus Replication , Animals , Humans , Rats , Hepatitis E virus/genetics , Hepatitis E virus/classification , Hepatitis E virus/physiology , Cell Line, Tumor , Hepatitis E/virology , Genotype , Genome, Viral , Carcinoma, Hepatocellular/virology , RNA, Viral/genetics , Hepatocytes/virology
6.
J Vet Med Sci ; 86(5): 524-528, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38556348

ABSTRACT

To conduct an epidemiological study of hepatitis E virus (HEV) in Japanese wild boars, we collected 179 serum and 162 fecal specimens from wild boars in eight Japanese prefectures; 39 of the serum samples (21.8%) were positive for anti-HEV IgG antibodies. RT-qPCR revealed HEV RNA in 11 serum samples (6.1%) and 5 fecal samples (3.1%). We obtained 412 bp of the viral genome sequences of ORF2 from five pairs of serum and fecal samples. All strains were subtype b in genotype 3 (HEV-3b) but separated into different clusters. We determined the entire genome sequence of HEV-3b strain WB0567 using a fecal specimen and isolated this strain by cell culture using PLC/PRF/5 cells. Eleven nucleotide mutations had occurred during virus replication. These results suggest that HEV-3b circulated uniformly among wild boars in Japan. Direct sequencing using a suspected animal's samples is indispensable for predicting original HEV nucleotide sequences.


Subject(s)
Feces , Genotype , Hepatitis E virus , Hepatitis E , Sus scrofa , Swine Diseases , Animals , Hepatitis E virus/genetics , Hepatitis E virus/isolation & purification , Hepatitis E virus/classification , Japan/epidemiology , Sus scrofa/virology , Hepatitis E/veterinary , Hepatitis E/virology , Hepatitis E/epidemiology , Feces/virology , Swine Diseases/virology , Swine Diseases/epidemiology , Swine , Phylogeny , Genome, Viral , RNA, Viral/genetics
7.
Vet Res Commun ; 48(3): 1803-1812, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38243141

ABSTRACT

Virus monitoring in small mammals is central to the design of epidemiological control strategies for rodent-borne zoonotic viruses. Synanthropic small mammals are versatile and may be potential carriers of several microbial agents. In the present work, a total of 330 fecal samples of small mammals were collected at two sites in the North of Portugal and screened for zoonotic hepatitis E virus (HEV, species Paslahepevirus balayani). Synanthropic small mammal samples (n = 40) were collected in a city park of Porto and belonged to the species Algerian mouse (Mus spretus) (n = 26) and to the greater white-toothed shrew (Crocidura russula) (n = 14). Furthermore, additional samples were collected in the Northeast region of Portugal and included Algerian mouse (n = 48), greater white-toothed shrew (n = 47), wood mouse (Apodemus sylvaticus) (n = 43), southwestern water vole (Arvicola sapidus) (n = 52), Cabrera's vole (Microtus cabrerae) (n = 49) and Lusitanian pine vole (Microtus lusitanicus) (n = 51). A nested RT-PCR targeting a part of open reading frame (ORF) 2 region of the HEV genome was used followed by sequencing and phylogenetic analysis. HEV RNA was detected in one fecal sample (0.3%; 95% confidence interval, CI: 0.01-1.68) from a synanthropic Algerian mouse that was genotyped as HEV-3, subgenotype 3e. This is the first study reporting the detection of HEV-3 in a synanthropic rodent, the Algerian mouse. The identified HEV isolate is probably the outcome of either a spill-over infection from domestic pigs or wild boars, or the result of passive viral transit through the intestinal tract. This finding reinforces the importance in the surveillance of novel potential hosts for HEV with a particular emphasis on synanthropic animals.


Subject(s)
Genotype , Hepatitis E virus , Hepatitis E , Phylogeny , Rodent Diseases , Animals , Hepatitis E virus/genetics , Hepatitis E virus/isolation & purification , Hepatitis E virus/classification , Portugal/epidemiology , Mice , Hepatitis E/veterinary , Hepatitis E/virology , Hepatitis E/epidemiology , Rodent Diseases/virology , Rodent Diseases/epidemiology , Feces/virology
8.
Vet Microbiol ; 263: 109275, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34798367

ABSTRACT

Rabbit hepatitis E virus (HEV) has been detected among rabbits and recently isolated from immunocompromised patients, suggesting zoonotic transmission. In this study, HEV infection among feral rabbits (Oryctolagus cuniculus) was assessed by detection of anti-HEV antibodies and HEV RNA. The prevalence of anti-HEV antibodies in sera was of 33 % (20/60) and HEV RNA was detected from only one of fecal swabs (1.7 %, 1/58). Furthermore, one naïve rabbit was intravenously inoculated with the suspension of the HEV-positive fecal specimen, exhibiting persistent HEV shedding in feces, intermittent viremia, seroconversion to anti-HEV IgM and IgG, and high alanine aminotransferase (ALT) values, indicating persistent HEV infection. The isolate JP-59 had a length of 7,282 bp excluding a poly (A) tail and possessed the characteristic 93 bp-insertion in ORF1. Phylogenetic analysis indicated that JP-59 formed a cluster with other rabbit HEV isolates from rabbits and human origin. The JP-59 shared the nucleotide sequence identities less than 87 % with other rabbit HEVs, suggesting that a novel rabbit HEV strain was circulating in Japan.


Subject(s)
Hepatitis E virus , Hepatitis E , Animals , Hepatitis Antibodies/blood , Hepatitis E/epidemiology , Hepatitis E/veterinary , Hepatitis E virus/classification , Hepatitis E virus/genetics , Hepatitis E virus/immunology , Hepatitis E virus/isolation & purification , Japan/epidemiology , Phylogeny , RNA, Viral/genetics , Rabbits
9.
Viruses ; 13(10)2021 09 28.
Article in English | MEDLINE | ID: mdl-34696377

ABSTRACT

To evaluate whether uterine injury caused by hepatitis E virus (HEV) infection is responsible for adverse pregnancy outcomes. HEV-infected female BALB/c mice were coupled with healthy male BALB/c mice at 0, 7, 14, 21, and 91 dpi to explore the uterine injury caused by HEV infection. Mice were euthanized after 10 days of copulation, and uteruses were collected for HEV RNA and antigen detection and histopathological analysis. Inflammatory responses; apoptosis; and estrogen receptor ɑ (ER-ɑ), endomethal antibody (ERAb), cytokeratin-7 (CK7), vimentin (VIM), and vascular endothelial growth factor (VEGF) expression levels were evaluated. After 10 days of copulation, miscarriage and nonpregnancy, as well as enlarged uteruses filled with inflammatory cytokines, were found in HEV-infected mice. HEV RNA and antigens were detected in the sera and uteruses of HEV-infected mice. Significant endometrial thickness (EMT) thinning, severe inflammatory responses, and aggravated apoptosis in the uteruses of HEV-infected mice that experienced miscarriage might contribute to adverse pregnancy outcomes. Furthermore, significantly suppressed ER-ɑ expression and increased ERAb, CK7, VIM, and VEGF expression levels were found in the uteruses of HEV-infected mice that had miscarried. However, uterine damage recovered after complete HEV clearance, and impaired fertility was improved. EMT injury, severe inflammatory responses, and aggravated apoptosis in the uterus caused by HEV infection are responsible for poor pregnancy outcomes.


Subject(s)
Genotype , Hepatitis E virus/genetics , Hepatitis E virus/pathogenicity , Hepatitis E/complications , Uterus/injuries , Uterus/virology , Abortion, Spontaneous , Animals , Disease Models, Animal , Female , Hepatitis Antibodies/immunology , Hepatitis E/virology , Hepatitis E virus/classification , Male , Mice , Mice, Inbred BALB C , Pregnancy , Pregnancy Outcome , Urogenital Abnormalities/virology , Uterus/abnormalities , Uterus/pathology , Virus Shedding
10.
Viruses ; 13(7)2021 07 09.
Article in English | MEDLINE | ID: mdl-34372535

ABSTRACT

The adverse relationship between viral hepatitis and pregnancy in developing countries had been interpreted as a reflection of retrospectively biased hospital-based data collection by the West. However, the discovery of hepatitis E virus (HEV) as the etiological agent of an epidemic of non-A, non-B hepatitis in Kashmir, and the documenting of the increased incidence and severity of hepatitis E in pregnancy via a house-to-house survey, unmasked this unholy alliance. In the Hepeviridae family, HEV-genotype (gt)1 from genus Orthohepevirus A has a unique open reading frame (ORF)4-encoded protein which enhances viral polymerase activity and viral replication. The epidemics caused by HEV-gt1, but not any other Orthohepevirus A genotype, show an adverse relationship with pregnancy in humans. The pathogenesis of the association is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the pregnant women including infection and damage to the maternal-fetal interface by HEV-gt1; vertical transmission of HEV to fetus causing severe fetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the pregnant women, promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of acute liver failure. (ALF). Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.


Subject(s)
Hepatitis E virus/genetics , Hepatitis E/complications , Hepatitis E/epidemiology , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/virology , Female , Genotype , Hepatitis E virus/classification , Humans , India/epidemiology , Infant, Newborn , Infectious Disease Transmission, Vertical , Liver/pathology , Liver/virology , Liver Failure, Acute/virology , Open Reading Frames , Pregnancy , RNA, Viral/genetics , Retrospective Studies , Virus Replication
11.
Viruses ; 13(6)2021 06 17.
Article in English | MEDLINE | ID: mdl-34204376

ABSTRACT

In European countries, autochthonous acute hepatitis E cases are caused by Hepatitis E Virus (HEV) genotype 3 and are usually observed as sporadic cases. In mid/late September 2019, a hepatitis E outbreak caused by HEV genotype 3 was recognized by detection of identical/highly similar HEV sequences in some hepatitis E cases from two Italian regions, Abruzzo and Lazio, with most cases from this latter region showing a link with Abruzzo. Overall, 47 cases of HEV infection were finally observed with onsets from 8 June 2019 to 6 December 2019; they represent a marked increase as compared with just a few cases in the same period of time in the past years and in the same areas. HEV sequencing was successful in 35 cases. The phylogenetic analysis of the viral sequences showed 30 of them grouped in three distinct molecular clusters, termed A, B, and C: strains in cluster A and B were of subtype 3e and strains in cluster C were of subtype 3f. No strains detected in Abruzzo in the past years clustered with the strains involved in the present outbreak. The outbreak curve showed partially overlapped temporal distribution of the three clusters. Analysis of collected epidemiological data identified pork products as the most likely source of the outbreak. Overall, the findings suggest that the outbreak might have been caused by newly and almost simultaneously introduced strains not previously circulating in this area, which are possibly harbored by pork products or live animals imported from outside Abruzzo. This possibility deserves further studies in this area in order to monitor the circulation of HEV in human cases as well as in pigs and wild boars.


Subject(s)
Disease Outbreaks , Genotype , Hepatitis E virus/classification , Hepatitis E virus/genetics , Hepatitis E/epidemiology , Hepatitis E/transmission , Adult , Aged , Aged, 80 and over , Animals , Female , Hepatitis E/virology , Hepatitis E virus/pathogenicity , Humans , Italy/epidemiology , Male , Middle Aged , Phylogeny , Pork Meat/virology , RNA, Viral , Risk Factors , Sus scrofa/virology , Swine , Swine Diseases/transmission , Swine Diseases/virology
12.
Viruses ; 13(7)2021 06 29.
Article in English | MEDLINE | ID: mdl-34209729

ABSTRACT

Pigs are suspected to be a major source of zoonotic hepatitis E virus (HEV) infection in industrialized countries, but the transmission route(s) from pigs to humans are ill-defined. Sequence comparison of HEV isolates from pigs with those from blood donors and patients in 372 samples collected in the Netherlands in 1998 and 1999 and between 2008 and 2015 showed that all sequences were genotype 3 except for six patients (with travel history). Subgenotype 3c (gt3c) was the most common subtype. While the proportion of gt3c increased significantly between 1998 and 2008, it remained constant between 2008 and 2015. Among the few circulating HEV subtypes, there was no difference observed between the human and the pig isolates. Hepatitis E viruses in humans are very likely to originate from pigs, but it is unclear why HEV gt3c has become the predominant subtype in the Netherlands.


Subject(s)
Blood Donors , Genotype , Hepatitis E virus/genetics , Hepatitis E/epidemiology , Sequence Analysis, DNA , Swine/virology , Animals , Hepatitis E/virology , Hepatitis E virus/classification , Humans , Netherlands/epidemiology , Phylogeny , RNA, Viral/genetics , Sus scrofa/virology , Swine Diseases/virology , Viral Zoonoses/transmission
13.
Viruses ; 13(6)2021 06 03.
Article in English | MEDLINE | ID: mdl-34205182

ABSTRACT

Hepatitis E is an emerging viral disease that is the leading cause of viral hepatitis in the world. The vast majority of hepatitis E cases in developed countries are caused by zoonotic genotypes 3 and 4 of hepatitis E virus (HEV) for which pig and wild boar and to lesser extent rabbits are the main reservoir. According to recent reports rabbits are a source of human HEV infection and highlight the risk of zoonotic foodborne transmission. Here we report the molecular analysis of a novel HEV strain identified in a rabbit during a countrywide surveillance of rabbits and hares in Germany, 2016. The analysis of the complete genome reveals characteristics of a putative novel recombinant subtype of the species Orthohepevirus A within the clade of genotype 3 but not closely related to any known subtypes. Importantly, the genome of this strain possesses a nucleotide exchange in the overlapping region of open reading frames ORF2/ORF3 interfering with a broadly applied diagnostic real-time RT-PCR. In conclusion, a new type of HEV strain was identified in a German rabbit with atypical and novel sequence characteristics.


Subject(s)
Genotype , Hares/virology , Hepatitis E virus/classification , Hepatitis E virus/genetics , Hepatitis E/veterinary , Zoonoses/virology , Animals , Genome, Viral , Germany/epidemiology , Hepatitis E/epidemiology , Hepatitis E virus/isolation & purification , Open Reading Frames , Phylogeny , RNA, Viral/genetics , Rabbits , Sequence Analysis, DNA , Zoonoses/epidemiology
14.
Viruses ; 13(6)2021 06 19.
Article in English | MEDLINE | ID: mdl-34205456

ABSTRACT

The wild boar is the most important reservoir of zoonotic HEV-3 strains among different wildlife species. The aim of the study was subtype identification of wild boar HEV-3 strains circulating in Poland. Wild boar liver was used in the study in the form of homogenates prepared from 57 samples positive for HEV in a real-time RT-PCR. These samples were collected from juvenile and adult wild boars hunted in the jurisdictions of different Regional Directorates of State Forests (RDSF) across Poland. Subtype identification of detected HEV strains was based on a phylogenetic analysis of the most conserved HEV ORF2 genome fragment. Out of 57 tested samples, consensus HEV ORF2 sequences of 348 bp were obtained for 45 strains. Nineteen strains were identified and belonged to the HEV gt 3a and 3i subtypes, whereas 26 were not assigned to any virus subtype. HEV gt 3i strains prevailed in the Polish wild boar population, 16 of such were identified, and they were significantly more often observed in the RDSF Katowice area (χ2 = 28.6, p = 0.027 (<0.05)) compared to other regions of the country. Circulation of 3a strains was limited only to the RDSF Gdansk territory (χ2 = 48, p = 0.000 (<0.05)). The virus strains detected in the Polish population of wild boars representing previously identified HEV subtypes in wild boars, pigs, or humans in Europe are of epidemiological importance for public health.


Subject(s)
Genetic Variation , Genotype , Hepatitis E virus/classification , Hepatitis E virus/genetics , Hepatitis E/veterinary , Swine Diseases/epidemiology , Swine Diseases/virology , Animals , Cross-Sectional Studies , Phylogeny , Phylogeography , Poland/epidemiology , Public Health Surveillance , Swine
15.
BMC Vet Res ; 17(1): 232, 2021 Jun 30.
Article in English | MEDLINE | ID: mdl-34193126

ABSTRACT

BACKGROUND: Hepatitis E virus (HEV) is agent causing hepatitis worldwide. Originally considered to be limited to developing countries, this virus was also detected in developed countries. In recent years an increasing number of reports indicate that farmed domestic pigs are widely infected with HEV in several European countries. The HEV status in Slovakia is still missing. RESULTS: In this study, the circulation of HEV among domestic swine in Slovakia and genetic diversity of the virus was studied. Overall HEV RNA was detected in 53/388 (13.7, 95% CI: 10.40-17.48%) pig rectal swabs in five production stages (age categories) with statistically significant differences among all the stages. The highest HEV prevalence was observed in weaners 24/81 (29.6, 95% CI: 19.99-40.81%) and then significantly declined in growers and fatteners. No HEV was detected in suckling piglets and sows. Twenty-eight partial sequences of ORF1 (242 bp) and seventeen of ORF2 (304 bp) were analysed. Phylogenetic analysis and p-distance comparisons confirmed in both ORFs that all Slovak HEV sequences belong to the genotype HEV-3, major clade 3abchij with higher identity to 3a and 3i subtypes. Three sequences were outside of all lastly updated HEV-3 subtypes. CONCLUSION: This is the first report to fill the information gap about HEV infection in pigs in Slovakia. The results suggested a lower prevalence of HEV in Slovak pig farms than observed in other European countries. While most HEV isolates were typed as HEV-3 clade 3abchij, three sequences were unclassified.


Subject(s)
Hepatitis E virus/classification , Hepatitis E virus/genetics , Hepatitis E/veterinary , Age Factors , Animals , Genetic Variation , Hepatitis E/epidemiology , Open Reading Frames/genetics , Phylogeny , Slovakia/epidemiology , Sus scrofa , Swine , Swine Diseases/virology
16.
Viruses ; 13(5)2021 05 17.
Article in English | MEDLINE | ID: mdl-34067873

ABSTRACT

People who use crack-cocaine (PWUCC) have numerous vulnerabilities and pose a challenge to health and social assistance services. The exposure to pathogens and risk situations occur differently according to each individual, region and social group. This study identified the presence, genotypes and factors associated with hepatitis E virus (HEV) exposure among a community-recruited cohort of 437 PWUCC in northern Brazil. Epidemiological information was collected through community-based assessments and interviews. Thereafter, blood and fecal samples were collected and tested for HEV using an immunoenzymatic assay, and the genotype was identified by PCR. Logistic regressions were used to identify the risk factors independently associated with exposure to HEV. In total, 79 (18.1%) PWUCC were exposed to HEV: 73 (16.7%) for IgG and six for IgG + IgM. HEV RNA was detected in six fecal samples and in two blood samples from PWUCC with IgM + IgG. Subtype 3c was identified in all of the samples. The factors associated with exposure to HEV were low monthly income, unstable housing (e.g., homelessness), crack-cocaine use ≥40 months, and the shared use of crack-cocaine equipment. The current study provides unique initial insights into HEV status and risk factors among PWUCC in a remote area in Brazil, with diverse implications for urgently improved diagnosis, prevention, and treatment intervention needs.


Subject(s)
Crack Cocaine , Drug Users , Hepatitis E virus , Hepatitis E/epidemiology , Hepatitis E/transmission , Adolescent , Adult , Brazil/epidemiology , Cross-Sectional Studies , Female , Genotype , Geography, Medical , Hepatitis E/virology , Hepatitis E virus/classification , Hepatitis E virus/genetics , Humans , Male , Middle Aged , Phylogeny , Public Health Surveillance , Young Adult
17.
J Med Virol ; 93(11): 6267-6277, 2021 11.
Article in English | MEDLINE | ID: mdl-34076903

ABSTRACT

Hepatitis E virus (HEV) is the major pathogen of viral hepatitis. However, the understanding of the HEV life cycle is limited. In the present study, cells were separately infected with nonenveloped HEV (derived from feces or bile) or quasi-enveloped HEV (derived from the cell culture after serial passages, eHEV) and observed by confocal fluorescence microscopy to investigate the life cycle of HEV. HEV finished its binding and entry into host cells at first 6 h postinoculation (hpi). Cells inoculated with eHEV showed less infectivity than cells inoculated with nonenveloped HEV. Newly synthesized progeny virions were released into the supernatant of cell cultures from 48 hpi. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis results showed that the supernatant's progeny viruses were infectious even after five serial passages. These results show the significant difference between nonenveloped HEV and eHEV, which will provide novel insights into the HEV replication cycle. The efficient cell culture of HEV will promote the development of anti-HEV drugs and vaccines.


Subject(s)
Hepatitis E virus/physiology , Virus Replication , A549 Cells , Carcinoma, Hepatocellular , Cell Line , Cell Line, Tumor , Hepatitis E/virology , Hepatitis E virus/classification , Humans , Liver Neoplasms , Microscopy, Fluorescence/methods , Viral Envelope , Virion/physiology
18.
Jpn J Infect Dis ; 74(6): 573-575, 2021 Nov 22.
Article in English | MEDLINE | ID: mdl-33952773

ABSTRACT

The human hepatocarcinoma cell line PLC/PRF/5 is susceptible to hepatitis E virus (HEV) infection and is used for HEV isolation. It is difficult to use the cell line for this purpose directly from fecal specimens of swine or wild boar contaminated with porcine sapelovirus (PSV) because PSV infection results in rapid and extensive cytopathic effects in PLC/PRF/5 cells, interrupting the growth of HEV. Herein, we used a PSV infection-resistant cell line, N1380, derived from PLC/PRF/5 cells, and successfully isolated a HEV-4b strain from a PSV-positive swine fecal specimen. Our results indicated that N1380 cells are a useful tool for the isolation of HEV from swine or wild boar fecal specimens, even when the cells are co-infected with PSV.


Subject(s)
Feces/virology , Hepatitis E virus/classification , Hepatitis E virus/isolation & purification , Hepatitis E/diagnosis , Swine Diseases , Animals , Cell Line , Hepatitis E/veterinary , Hepatitis E virus/genetics , Picornaviridae/isolation & purification , Picornaviridae Infections/diagnosis , Swine
19.
PLoS Pathog ; 17(2): e1009367, 2021 02.
Article in English | MEDLINE | ID: mdl-33617602

ABSTRACT

Genotype 3 Hepatitis E virus (HEV-3) is an emerging threat for aging population. More than one third of older infected patients develops clinical symptoms with severe liver damage, while others remain asymptomatic. The origin of this discrepancy is still elusive although HEV-3 pathogenesis appears to be immune-mediated. Therefore, we investigated the role of CD8 T cells in the outcome of the infection in immunocompetent elderly subjects. We enrolled twenty two HEV-3-infected patients displaying similar viral determinants and fifteen healthy donors. Among the infected group, sixteen patients experienced clinical symptoms related to liver disease while six remained asymptomatic. Here we report that symptomatic infection is characterized by an expansion of highly activated effector memory CD8 T (EM) cells, regardless of antigen specificity. This robust activation is associated with key features of early T cell exhaustion including a loss in polyfunctional type-1 cytokine production and partial commitment to type-2 cells. In addition, we show that bystander activation of EM cells seems to be dependent on the inflammatory cytokines IL-15 and IL-18, and is supported by an upregulation of the activating receptor NKG2D and an exuberant expression of T-Bet and T-Bet-regulated genes including granzyme B and CXCR3. We also show that the inflammatory chemokines CXCL9-10 are increased in symptomatic patients thereby fostering the recruitment of highly cytotoxic EM cells into the liver in a CXCR3-dependent manner. Finally, we find that the EM-biased immune response returns to homeostasis following viral clearance and disease resolution, further linking the EM cells response to viral burden. Conversely, asymptomatic patients are endowed with low-to-moderate EM cell response. In summary, our findings define immune correlates that contribute to HEV-3 pathogenesis and emphasize the central role of EM cells in governing the outcome of the infection.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Hepatitis E virus/classification , Hepatitis E/pathology , Immunologic Memory/immunology , Receptors, CXCR3/metabolism , Aged , Case-Control Studies , Cytokines/metabolism , Female , Genotype , Hepatitis E/immunology , Hepatitis E/virology , Hepatitis E virus/genetics , Hepatitis E virus/immunology , Humans , Male , Middle Aged
20.
Viruses ; 13(2)2021 02 01.
Article in English | MEDLINE | ID: mdl-33535675

ABSTRACT

Hepatitis E virus (HEV), a major cause of viral hepatitis worldwide, is considered an emerging foodborne zoonosis in Europe. Pigs (Sus scrofa domestica) and wild boars (S. scrofa) are recognized as important HEV reservoirs. Additionally, HEV infection and exposure have been described in cervids. In Norway, HEV has been identified in pigs and humans; however, little is known regarding its presence in wild ungulates in the country. We used a species-independent double-antigen sandwich ELISA to detect antibodies against HEV in the sera of 715 wild ungulates from Norway, including 164 moose (Alces alces), 186 wild Eurasian tundra reindeer (Rangifer tarandus tarandus), 177 red deer (Cervus elaphus), 86 European roe deer (Capreolus capreolus), and 102 muskoxen (Ovibos moschatus). The overall seroprevalence was 12.3% (88/715). Wild reindeer had the highest seropositivity (23.1%, 43/186), followed by moose (19.5%, 32/164), muskoxen (5.9%, 6/102), and red deer (4%, 7/177). All roe deer were negative. According to our results, HEV is circulating in wild ungulates in Norway. The high seroprevalence observed in wild reindeer and moose indicates that these species may be potential reservoirs of HEV. To the authors' knowledge, this is the first report of HEV exposure in reindeer from Europe and in muskoxen worldwide.


Subject(s)
Animals, Wild/blood , Antibodies, Viral/blood , Hepatitis E virus/immunology , Hepatitis E/veterinary , Ruminants/blood , Animals , Animals, Wild/virology , Deer/blood , Deer/virology , Hepatitis E/blood , Hepatitis E/epidemiology , Hepatitis E virus/classification , Hepatitis E virus/genetics , Norway/epidemiology , Reindeer/blood , Reindeer/virology , Ruminants/virology , Seroepidemiologic Studies , Sus scrofa/blood , Sus scrofa/virology , Swine , Swine Diseases/blood
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